04724nas a2201189 4500008004100000022001400041245009300055210006900148260001300217300001200230490000700242520135800249100001801607700002101625700002001646700002501666700002201691700001901713700002301732700002801755700002501783700002101808700001701829700001601846700002201862700002101884700001601905700002001921700002101941700002301962700002201985700002102007700002402028700002102052700002402073700001902097700002502116700002402141700002102165700002502186700002402211700002402235700001402259700001702273700002202290700002302312700001902335700001802354700002502372700002302397700001802420700001702438700001902455700002202474700002402496700001702520700002602537700002002563700001802583700003002601700001602631700001802647700002702665700001802692700002102710700002602731700001902757700001702776700002202793700002202815700002002837700002302857700002102880700002202901700001902923700002002942700002302962700001802985700002803003700001603031700002603047700002103073700002203094700002203116700002803138700002203166700002503188700002103213700002403234700001903258700002303277700002003300700002003320700002603340700002203366700002403388700002303412700001903435700002203454700002203476856003603498 2016 eng d a1468-624400aMeta-analysis of genome-wide association studies of HDL cholesterol response to statins.0 aMetaanalysis of genomewide association studies of HDL cholestero c2016 Dec a835-8450 v533 a
BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.
METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.
CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
1 aPostmus, Iris1 aWarren, Helen, R1 aTrompet, Stella1 aArsenault, Benoit, J1 aAvery, Christy, L1 aBis, Joshua, C1 aChasman, Daniel, I1 ade Keyser, Catherine, E1 aDeshmukh, Harshal, A1 aEvans, Daniel, S1 aFeng, QiPing1 aLi, Xiaohui1 aSmit, Roelof, A J1 aSmith, Albert, V1 aSun, Fangui1 aTaylor, Kent, D1 aArnold, Alice, M1 aBarnes, Michael, R1 aBarratt, Bryan, J1 aBetteridge, John1 aBoekholdt, Matthijs1 aBoerwinkle, Eric1 aBuckley, Brendan, M1 aChen, Y-D, Ida1 ade Craen, Anton, J M1 aCummings, Steven, R1 aDenny, Joshua, C1 aDubé, Marie, Pierre1 aDurrington, Paul, N1 aEiriksdottir, Gudny1 aFord, Ian1 aGuo, Xiuqing1 aHarris, Tamara, B1 aHeckbert, Susan, R1 aHofman, Albert1 aHovingh, Kees1 aKastelein, John, J P1 aLauner, Leonore, J1 aLiu, Ching-Ti1 aLiu, Yongmei1 aLumley, Thomas1 aMcKeigue, Paul, M1 aMunroe, Patricia, B1 aNeil, Andrew1 aNickerson, Deborah, A1 aNyberg, Fredrik1 aO'Brien, Eoin1 aO'Donnell, Christopher, J1 aPost, Wendy1 aPoulter, Neil1 aVasan, Ramachandran, S1 aRice, Kenneth1 aRich, Stephen, S1 aRivadeneira, Fernando1 aSattar, Naveed1 aSever, Peter1 aShaw-Hawkins, Sue1 aShields, Denis, C1 aSlagboom, Eline1 aSmith, Nicholas, L1 aSmith, Joshua, D1 aSotoodehnia, Nona1 aStanton, Alice1 aStott, David, J1 aStricker, Bruno, H1 aStürmer, Til1 aUitterlinden, André, G1 aWei, Wei-Qi1 aWestendorp, Rudi, G J1 aWhitsel, Eric, A1 aWiggins, Kerri, L1 aWilke, Russell, A1 aBallantyne, Christie, M1 aColhoun, Helen, M1 aCupples, Adrienne, L1 aFranco, Oscar, H1 aGudnason, Vilmundur1 aHitman, Graham1 aPalmer, Colin, N A1 aPsaty, Bruce, M1 aRidker, Paul, M1 aStafford, Jeanette, M1 aStein, Charles, M1 aTardif, Jean-Claude1 aCaulfield, Mark, J1 aJukema, Wouter1 aRotter, Jerome, I1 aKrauss, Ronald, M uhttps://chs-nhlbi.org/node/7358